A glycosylated hemoglobin above 6% is associated with a high risk of developing cystic fibrosis–related diabetes and a lower probability of weight gain in both adults and children with cystic fibrosis

The classical glycosylated hemoglobin (A1C) threshold of 6.5% is an insensitive screening test for cystic fibrosis (CF)—related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD, and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1). We studied the cross-sectional and longitudinal associations between A1C, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5±4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including oral glucose tolerance test (OGTT). For the onset of OGTT-defined CFRD, optimal A1C threshold was 5.9% in adults (sensitivity: 67%; specificity: 71%) and 5.7% for children (sensitivity: 60%; specificity: 47%). Kaplan-Meier analysis of progression to CFRD according to baseline A1C showed an increased risk of developing CFRD for A1C ≥6.0% in adults (p=0.002) and ≥5.5% in children (p=0.012). Temporal changes in BMI and FEV1 according to baseline A1C in adults were assessed with a linear mixed-effect model. BMI significantly increased over time in subjects with a baseline A1C <6.0%, but those with an A1C ≥6.0% gained significantly less weight over time (p=0.05). There was no difference in FEV1 according to baseline A1C category. An A1C above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.